In Vitro Assessment of a MAF‐1A‐Derived Peptide Against Candida parapsilosis : Antifungal Potency, Trypsin Stability, and Hemolytic Safety

Candida parapsilosis (C. parapsilosis) has caused more infections in recent years, and resistance to conventional antifungal agents is also rising. This study evaluated the antifungal potential of a newly designed MAF-1A-derived peptide against C. parapsilosis. Four derivatives were chemically synthesized and structurally characterized. Our hybrid method included the use of computational tools for hydrophobic optimization, amphipathic α-helix stabilization, and peptide-membrane interaction prediction together with experimental validations. We synthesized four designed derivatives (8KGF7, 9GIF6, 10KLF6, and 10GIF6) by Fmoc-based solid-phase chemistry. Its antifungal activity against C. parapsilosis was assessed using the broth microdilution assay. Trypsin stability was evaluated by incubating 10KLF6 with trypsin followed by measurement of residual antifungal activity. Hemolytic safety was assessed using human red blood cells via hemolytic activity assays. The results demonstrated that 10KLF6 exhibited up to 15-fold higher antifungal activity against C. parapsilosis compared to MAF-1A. Additionally, 10KLF6 retained more than 20% of its antifungal activity after 100 min of trypsin digestion and showed low hemolytic toxicity. Collectively, 10KLF6 possesses potent antifungal activity as well as favorable stability and safety profiles against C. parapsilosis, which supports its further exploration as a promising candidate for the development of potent and stable antifungal peptide agents.